Peanut allergy is one of the most serious of the immediate hypersensitivity reactions to foods in terms of persistence and severity of the reaction and appears to be a growing problem. Due to the persistence of this reaction and the lack of effective treatment, allergen-specific immunotherapy (IT) is currently being examined as a treatment option. The goal of our laboratory is to develop specific and effective immunotherapy for patients suffering from peanut hypersensitivity. The T lymphocyte plays a central role in the events that lead to the development of peanut hypersensitivity and allergic disease in general. Based on a novel idea that the storage proteins in soybeans would share enough amino acid homology with the respective peanut allergens to down regulate peanut-specific T cells, we have utilized soybean protein IT in a peanut allergic mouse model to desensitize the animals to peanuts. The soybean IT treated animals had a significant reduction of clinical symptoms after peanut challenges compared to placebo treated animals. This innovative application is designed to utilize our extensive knowledge of the allergens involved in peanut hypersensitivity to devise an immunotherapeutic approach that would lower the risk of anaphylactic reactions and would down regulate peanut-specific T cells in peanut-allergic patients. Based on the known amino acid homology in the seed storage proteins in legumes, our hypothesis is that soybean IT will desensitize patients with peanut allergic reactions. We will test this hypothesis by two specific aims: specific aim 1: Identify the molecular mechanism of peanut-specific T-cell response in peanut-allergic mice desensitized with soybean IT and specific aim 2: Desensitize peanut-allergic adults with soybean IT and determine the molecular mechanism of the peanut-specific T-cell response during IT. In peanut-allergic mice, we will delineate the role of exposure to soybean IT on subsequent T-cell response/anergy to peanuts by: (a) examining the profile of peanut-specific Thl/Th2 lymphocytes; (b) analyzing both early events of T-cell activation and later events such as induction and activation of transcription factors and cytokine secretion, and (c) characterizing the regulatory T cells induced following soybean IT. In peanut-allergic adults, we will determine whether soybean IT given to patients with peanut allergy results in the down regulation of the specific lymphocyte response to peanuts and the molecular mechanism of this response. An understanding of the molecular mechanisms of peanut allergy is vital to ensure the eventual, successful treatment of peanut-allergic patients. If soybean IT in peanut allergic patients is effective, the treatment would provide an immediate therapeutic option.